Prognostic factors and survival outcomes of urgent inpatient chemotherapy for relapsed/refractory lymphoma in the modern era

Abstract

Abstract Introduction: Patients (pts) with relapsed/refractory (RR) lymphoma frequently require urgent inpatient (inpt) admission for symptomatic disease progression (PD) and may need chemotherapy (chemo) for disease control. Clinical efficacy and long-term outcomes of these treatments are not well known. In this retrospective study we evaluate the outcomes and prognostic factors for survival following urgent inpt chemo. Methods: Adult pts aged ≥18 years (n=96) with RR lymphoma who received unplanned inpt chemo at the Cleveland Clinic from 01/2021 to 10/2023 were included in the study. Pts admitted for planned chemo were excluded. Pt and disease characteristics were analyzed. Outcomes assessed include inpt chemo continuation at 3 months (mo) post-discharge, response rates, overall survival (OS), progression-free survival (PFS), and 30-day mortality after chemo. OS and PFS were estimated using the Kaplan-Meier method, and associated prognostic factors were compared using the log-rank test in univariate analysis (UVA). The multivariate Cox model identified variables associated with survival and logistic regression was used to determine predictors for complete response (CR) and 30-day mortality. Results: The median age at admission was 62 years (range 23–86). Most were male (59%) and Caucasian (82%). Charlson comorbidity scores were 0–2 in 38%, 3–4 in 33%, and ≥5 in 29%. Most pts had poor performance status (ECOG ≥ 2, 56%), stage III-IV disease (63%), and aggressive B-cell lymphoma (69%). Fourteen percent had T-cell lymphoma. Most (69%) received ≤2 lines of therapy, with prior chimeric antigen receptor (CAR)-T (14%) and/or autologous stem cell transplant (ASCT) (9%) being infrequent. Primary refractory disease was in 42% of pts, and 57% were refractory to the last line of therapy. The median hospital stay was 10 days (range 2–59). Pre-chemo low albumin (<4 g/dL), glomerular filtration rate (GFR ≤ 60 mL/min/1.73m2), hemoglobin (Hb <10 g/dl), and platelets (PLT <100 k/µL) were noted in 76%, 20%, 43%, and 39% of pts, respectively. Chemo regimens include methotrexate/cytarabine-based (n=25), conventional chemo (n=23), polatuzumab-based (n=18), gemcitabine-based (n=15) and bispecific/monoclonal antibody/antibody drug conjugate (n=15). Dose reduction was required for 26% of pts, and 57% received (peg)filgrastim. About 27% required intensive care unit (ICU) care for complications like sepsis (17%). The 30-day readmission and emergency visit rates were 55% and 34% respectively. More than half (53%) continued chemo post-discharge, but only 9 pts (9.8%) remained on treatment at 3 mo. The overall response rate (ORR) was 21% (10% CR and 11% partial response), and 48% had PD. At a median follow-up of 22.7 mo (range 0.6–49.8) for surviving pts, median OS was 3.25 mo (95% CI:2.56–4.76) and PFS was 1.87 mo (95% CI:1.41–2.33). Three-mo PFS and OS rates were 29% (95% CI:21–39) and 53% (95% CI:44-64), respectively. At the time of analysis, 80% were deceased, 12% alive without PD and 30-day mortality rate was 16%. On UVA analysis, pts with low albumin (pOs=.0097, pPFS=.018), refractory to last regimen (pOS=.014, pPFS=.0006), prior CAR T (pOS=.005, pPFS=.0008), and low PLT (pOS=.004, pPFS=.013) had inferior OS and PFS. Primary refractory disease (p=.002) and sepsis post chemo (p=.039) predicted worse PFS. Prior ASCT (p=.024), low Hb (p=.035), ≥4 prior therapies (p=.046), no (peg)filgrastim use (p=.016), and low GFR (p=.048) resulted in poor OS. On multivariate analysis, refractoriness to last regimen (hazard ratio [HR]OS=1.78 [95% CI:1.09-2.91; p=.02]; HRPFS=2.08; [1.31-3.30; p=.002]) and prior CAR-T (HROS=2.07; [1.10-3.89; p=.02]; HRPFS=2.60; [1.37-4.93; p=.003]) significantly impacted survival. Low albumin (HR=1.84; [1.01-3.38; p=.05]) and GFR <=60 (HROS=1.79; [1.00-3.21; p=.05]) adversely impacted OS. Pts with primary refractory disease (odds ratio (OR)=0.055; [0.011-0.287; p=.0006]) and low PLT (OR=0.085; [0.014-0.506; p=.007]) had lower chance of achieving a CR. Higher 30-day mortality was observed with low GFR (OR=4.17; [1.16–15.01; p=.03]) and ICU stay (OR=6.27; [1.88–20.96; p=.003]). Conclusion: Our analysis shows poor outcomes in RR lymphoma pts following urgent inpt chemo treatment with median OS<4 months. Impaired organ function and chemo-refractory disease were predictive for survival and response to inpt chemo. In an era of rising healthcare costs, optimal pt selection is essential to maximize the clinical benefits of such interventions.